LOCALIZATION OF TUMOR-REACTIVE LYMPH-NODE LYMPHOCYTES IN-VIVO USING RADIOLABELED MONOCLONAL-ANTIBODY

Background. Lymph node lymphocytes vary in their responsiveness to tum or. A technique has been developed that uses radiolabeled monoclonal a ntibody (MoAb) against the tumor-associated mucin, TAG-72, and a gamma -detecting probe by which lymph nodes containing microscopic tumor and /or shed TAG-72 can be identified in vivo. The immunologic characteris tics of these lymph nodes were examined. Methods. Patients with colon cancer received I-125-labeled MoAb CC49 by intravenous injection preop eratively. During laparotomy lymph nodes that appeared normal on inspe ction and palpation but which contained radiolabeled MoAb were identif ied using a hand-held gamma-detecting probe. These lymph nodes and oth er lymph node and tumor specimens were resected for analysis. Results. Lymph nodes identified by the probe were found by immunohistochemical studies to contain microscopic tumor and/or shed antigen associated w ith germinal centers. They were characterized by greater CD4(+):CD8(+) ratios, rates of expansion, and cytolytic activity compared with lymp hocytes from lymph nodes with macroscopic tumor, noninvolved lymph nod es, and tumors. All lymph node lymphocytes identified by the probe dem onstrated significant proliferative responses to autologous tumor and, in contrast to lymphocytes from noninvolved lymph nodes, significant proliferative responses to allogeneic TAG-72(+) tumor cells and to sol uble TAG-72(+) mucin. Conclusions. By locating lymph nodes with micros copic tumor and/or shed antigen, the use of radiolabeled MoAb in vivo can be used to reproducibly identify tumor-reactive lymph node lymphoc ytes. This technique may be useful in identifying cells for use in ado ptive immunotherapy programs and in studying the regulation of immune responses in vivo.